Will Rogers once stated: “Personally I have always felt that the best doctor in the world is the Veterinarian, for he can't ask his patients ‘What is the matter . . . ?’, he's just got to know.” Since the inception of veterinary medicine, the veterinarian has been forced to rely on a keen sense of observation and assessment of clinical parameters for evaluation of his/her patients in the diagnosis and treatment of disease. Over the years and often on the heels of human medicine, many clinical tools, diagnostic and/or prognostic parameters and modalities have developed for assessment of these clinical parameters and hence evaluation of the health status of an animal.
Heart rate variability (HRV) generally refers to the beat-to beat fluctuations in heart rate (e.g., variation in R-R interval) that occur as a normal physiological response, e.g., an internal response to neuronal or endocrine influence, or variations in heart rate that occur in response to external stimuli. In general, heart rate variability reflects non-invasively the autonomic nervous system activity, e.g., the sympathetic and parasympathetic influences upon heart beat rate and rhythm.
In human medicine, the most studied body systems in HRV analysis are: the respiratory system and its effect on HRV known as respiratory sinus arrhythmia; the vasomotor system and baroreceptor variation in heart rate and blood pressure, e.g., Mayer waves; the thermoregulatory system; the renin-angiotensin system and the central nervous system. At present, in human medicine, it can generally be stated that greater variability in heart rate indicates a better state of health for the autonomic nervous and/or cardiac systems (see, e.g., petrus.upc.es/wwwdib/bio/heart_rat_var/pruebas/hrv1.html).
In human medicine, heart rate variability has been studied or used in the prognosis of sudden cardiac death and for the diagnosis of subacute and potentially catastrophic illness. In U.S. Pat. No. 6,330,469 to Griffen et al., HRV has been used in a method to access the health status of premature newborn infants and for the early detection of catastrophic illness in a patient. Likewise, U.S. Pat. No. 5,105,354 to Nishimura discloses a method for evaluation of respiration and heart beat which permits one to forecast sudden infant death syndrome (SIDS).
Heart rate variability has also been used in human medicine as an indicator of exercise capacity. U.S. Pat. No. 6,301,499 to Carlson et al., discloses a method for correlation of VO2.sub.max with HRV for determining exercise capacity in patients with congestive heart failure (CHF). Tygesen et al. in “Intensive home-based exercise training in cardiac rehabilitation increases exercise capacity and heart rate variability” (Int J Cardiol. 2001 July; 79(2-3):175-82) disclose that intensive exercise training in cardiac rehabilitation increases exercise capacity and global HRV, which could be of prognostic significance.
Various systems for determination of and/or monitoring HRV in human patients have been described, see, e.g., U.S. Pat. No. 6,212,427 to Hoover which discloses a rather cumbersome apparatus designed to be worn by the patient comprised of an output device requiring a plurality of properly placed electrodes for generation of an electrical signal from the patient's heart.
In veterinary medicine, prior to the present invention, the limited attempts at utilization of heart rate variability have produced variable results. For example, in “Spectral analysis of circadian rhythms in heart rate variability of dogs” (Am J Vet Res. 2001 January; 62(1):37-42), Matsunaga et al. disclose that power spectral analysis of HRV may be useful as a noninvasive technique for assessing the effect of drugs on activity of the autonomic nervous system in dogs. Likewise, Kawase et al. in “Heart rate variability during massive hemorrhage and progressive hemorrhagic shock in dogs” (Can J Anaesth 2000 August: 47(8):807-14) disclose that HRV could be a valuable tool in assessing various degrees of hemorrhagic shock.
In food producing animals, heart rate variability has been studied in cattle with BSE (see, e.g., “Heart rate variability in BSE”, Vet Rec. 1996 December 21-28; 139(25):631) and during parturition in cattle (see, Jonker et al., “Characteristics of fetal heart rate changes during the expulsive stage of bovine parturition in relation to fetal outcome”, Am J Vet Res. 1996 September; 57(9): 1373-81).
Likewise, limited analysis of heart rate variability has been conducted in the horse. For example, Physick-Sheard et al. indicate that frequency and power spectral analysis of HRV may be a method for assessing exercise response to experimental manipulations and disease states in the horse (Physick-Sheard et al., “Frequency domain analysis of heart rate variability in horses at rest and during exercise”, Equine Vet J. 2000 May;32(3):253-62).
Kuwahara et al., and Thayer et al. report that the equine heart may be largely controlled by parasympathetic activity and disclose a decrease in HRV by training, rather than an expected increase as seen in human counterparts (See, Kuwahara et al., “Influence of training on autonomic nervous function in horses: evaluation by power spectral analysis of heart rate variability.”, Equine Vet J Suppl. 1999 July; 30:178-80; Thayer et al., “Heart rate variability in the horse by ambulatory monitoring”, Biomed Sci Instrum. 1997; 33:482-5; and also Thayer et al., “Heart rate variability during exercise in the horse.”, Biomed Sci Instrum. 1997; 34:246-51). Prior to the present invention, perhaps one of the more definitive works for heart rate variability in the horse set forth by Mark Bowen (Bowen, M., “Heart Rate Variability”, Cardiology of the Horse, Ch. 11: 161-76, 1999 W. B. Saunders (ed. by Celia Marr)), acknowledged the largely experimental nature of the use of this modality in the horse and notes that little work has been actually been done in the horse.
Moreover, much of the work done in animals cites confusing, if not disappointing results. For example, in “Heart rate variability in Doberman Pinschers with and without echocardiographic evidence of dilated cardiomyopathy” (Am J Vet Res. 2000 May; 61(5):506-11) Calvert & Jacobs disclose that HRV as a diagnostic tool in animals has important limitations and that better noninvasive tests of autonomic function are needed. Likewise, Calvert demonstrated that HRV analysis in the dog is confounded by pronounced sinus arrhythmia and may not have clinical utility as a diagnostic technique in dogs (see, “Heart rate variability”, Calvert, C. A., Vet Clin North Am Small Animal Pract. 1998 November: 28(6):1409-27, viii). See also, Minors & O'Grady, “Heart rate variability in the dog: is it too variable?”, Can J Vet Res. 1997 April; 61(2):134-44.
Animal studies with dogs at Ohio State University indicated that the low frequency component of the HRV spectrum (0.06-0.10 Hz), often used as an “accurate” reflection of sympathetic activity, does not correlate with interventions which enhance cardiac sympathetic drive, e.g., exercise and myocardial ischemia (which should elicit increases in the low-frequency power). In these studies, the low frequency power decreased rather than increased and, as such, does not accurately reflect changes in sympathetic activity (see, Houle & Billman, “Low-frequency component of the heart rate variability spectrum: a poor marker of sympathetic activity”, Am J Physiol. 1999 January: 276(1Pt2:H215-23). Thus, there still exists a need in the art for a device and method which enables convenient, accurate, and meaningful analysis of such HRV parameters in animals.
In addition, prior to the present invention there has been little to no work done with respect to HRV as a clinical tool for assessment and management of stress in animals, especially animals reared in confinement or for companion animals, e.g., in pets exposed to separation anxiety. Likewise, prior to the present invention, the art has been virtually devoid of information relative to providing effective non-invasive management of pain in animals utilizing HRV. Accordingly, there exists a need in the art for a device and method which enables a veterinarian, or other user, to accurately, conveniently and efficiently assess pain and well being in animals and for diagnosis of disease conditions and for clinical evaluation of efficacy of therapeutic measures to eliminate or manage the same.